This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza, a highly communicable acute respiratory disease, is one of the major infectious disease threats to the human population. Some of the challenges in developing an effective vaccine for influenza occur because influenza viruses exhibit change in genetic structure each season. None of the current vaccines offer protection in a way that accounts for this genetic change. VaxInnate has developed a cross-protective influenza A vaccine, VAX102, which is based on a recombinant protein expressed in E. coli. The main purpose of the study is to assess the safety, reactogenicity and tolerability of the VAX102 vaccine given as an injection into the muscle at 3 doses, 10 [unreadable]g, 33 [unreadable]g and 100 [unreadable]g. The vaccine will be given at Day 0 and a booster at Day 28 to healthy adults, 18-49 years of age. Additional purposes of the study are to assess the immune response to the VAX102 vaccine. Laboratory studies will be performed to evaluate safety and immune response. Subjects will be asked to keep a diary of local reactions (i.e., redness or swelling) and systemic symptoms such as pain and fatigue. Subjects will be followed frequently during the one month post each dose of study agent, and at other intervals during the 6 months following the first vaccine dose. Development of an alternative influenza vaccine that will be protective across multiple influenza seasons and will be produced in a method that will allow for rapid production is critical to global health.